The Lead CRA Blog

So true, and what’s perhaps even more devastating ...

2013-07-29T06:08:58.829-07:00

So true, and what’s perhaps even more devastating is that there’s been so little support to help the community rebuild.

moving services

Kelly, I'm glad to hear you have adopted this ...

2013-06-19T12:04:41.144-07:00

Kelly, I'm glad to hear you have adopted this best practice. Anything we can do to produce additional documentation and proof of increased oversight can be a a plus in this highly regulated industry. Thanks for your thoughts on the topic.

Hi Kelly, I am so glad you stopped by to check out...

2013-06-19T11:30:09.309-07:00

Hi Kelly, I am so glad you stopped by to check out the blog. Your background on the task force is very interesting to me and I would love to network further.

I welcome tangible metrics and I was glad to see the retrospective review of SDV vs. queries generated. An additional metric that I plan to explore on the ClinOpsToolkit, would be to also account for the amount of entry that happens prior to and during SDV when the monitor picks up on & flags safety or other data that has not been entered. Many items aren’t even queried in the system (just flagged for entry in the source document review instead). A significant amount of under-stated data revision (or entry) occurs because of attention, conversation, and action taken during the monitoring visit. I don't see any of this accounted for in the metrics Transcelerate provided.

For this blog, I am still looking for a guest contributor to write about the CRA perspective of risk-based monitoring, perhaps you would know someone who would be interested? Please email me.

I've written a response from the Trial Manager perspective for Risk-Based Monitoring at the ClinOpsToolkit blog. I'd love for you to check it out.

Finally, I'm not sure that I agree that all CRAs necessarily have evolved from 100% SDV to Site Managers, but I am delighted to hear of the progress your company has made with adaptive monitoring. I will be doing my part to assist that CRAs who read this blog hone the correct Site Manager skillset.

Hi Nadia, FOr our company it is good practice to h...

2013-06-19T10:25:13.473-07:00

Hi Nadia,
FOr our company it is good practice to have the investigator review and sign the monitor follow up letter as it shows good investigator oversight. We are not required to document this completion in our Monitor Reports though. I have had many audits and inspections where the auditors are quite impressed to see investigator reviews on everything and not only lab reports, ECG reports, source documents (monitor letters, DILs, newsletters, memos, etc).

Great Summary! I am a Senior Site Manager and I am...

2013-06-19T10:19:59.669-07:00

Great Summary!
I am a Senior Site Manager and I am involved in a task force for Risk Based / Adaptive Monitoring. I was fortunate to be involved in the Transcelerate Initiative for the Restrospective review of SDV vrs queries generated for critical data. It was quite fascinating. My company has a few studies with the Adaptive Monitoring Approach and so much can be reviewed centrally. It is important to have the large picture and ensure the site is following the protocol with no major deviations and that patient safety is #1. CRAs have evolved from 100% SDV workers to more in depth Site Managers.

Hi Marten, I've worked for several companies w...

2013-06-13T13:25:32.388-07:00

Hi Marten, I've worked for several companies where we sent physical letters on company-furnished letterhead. I've also worked for one sponsor who didn't require confirmation letters (only emails!). I believe that the letter is just an artifact to demonstrate the clinical record and show someone years later what happened in managing and overseeing the trial; whether it is paper or an electronic equivalent is completely arbitrary to me. I just want to be able to reconstruct what happened and the letter is a piece of that story and evidence.

My current company requires all investigators to sign and date each followup letter. At the subsequent visit the monitor confirms that the signature (indicating a review of the letter) is documented in the monitoring report. Are any of you working on trials with this requirement in the monitoring plan?

Thanks again to Shantanu and the Medidata "Ge...

2013-06-13T13:20:19.276-07:00

Thanks again to Shantanu and the Medidata "Geeks Talk Clinical" blog team for this summary of risk-based monitoring. The role of monitors has to change. The hypothesis is that data quality can be achieved without 100% SDV; it will be interesting to see this in practice.

I for one, still have a lot of questions about centralized monitoring, how to select which items to target for partial SDV (looking for different data patterns and risks), a discussion of other diverse monitoring methods, how will sponsors track their central monitoring efforts and reconcile that everything was completed (how will they leverage technology to do this?), etc.

I plan to address these questions and more in future blog posts here and at the Clinical Operations toolkit blog - stay tuned!

Are there really companies that won't allow yo...

2013-06-13T05:20:42.812-07:00

Are there really companies that won't allow you to send the follow up letter by email? After 4 years working with several companies I've never experienced that. Maybe it's because I'm working in Europe?

Nadia, this was a great post. I will keep your adv...

2013-05-22T11:57:06.595-07:00

Nadia, this was a great post. I will keep your advice in mind, as I am currently working to build the "introductions" that will allow us to fill the pipeline with more trials... Thank you for taking the time to craft an uber-useful pot.

I once read "the patient had chocolate covere...

2013-05-05T06:51:14.103-07:00

I once read "the patient had chocolate covered stool after last night's dinner"

I am using very little paper these days. My monit...

2013-05-01T05:49:32.178-07:00

I am using very little paper these days. My monitor notes are done on my computer. I love my medical calculator on my iPhone.

Two tools that I use are a scanner (either Neat or smart phone) in PDF for collecting copies of reg. docs. This is really efficient for a COV especially if you have eTMF. It is also handy if you are allowed to scan your receipts for your travel expense report.

I carry a small surge protector with 4 electrical ports and 2 USB ports. This thing has saved me so many times when I have a co-monitor and there aren't enough outlets.

Technology is great when it works. to prevent a disaster, I always back-up my computer before I travel. I travel with a flash drive and I back-up any new information I store on my computer to the flash drive.

if source documents are not provided, how do you e...

2013-04-27T09:25:14.690-07:00

if source documents are not provided, how do you ensure that the appropriate information is being captured?

Hello, Can I get a resource to a sample questionna...

2013-04-10T02:26:01.245-07:00

Hello, Can I get a resource to a sample questionnaire to ask the PI, in a clinical investigator selection and qualification visit

Perhaps you can shed some light on an issue at our...

2013-04-04T08:47:07.016-07:00

Perhaps you can shed some light on an issue at our site. I'm the Research Practice Manager for a research site affiliated with a much larger medical practice. Our physicians use either iPads or laptops to access the practice's EMR system when meeting with their patients. Our research side still uses paper source documents because, overall, we find it easier to provide monitors paper charts of study-related subject source with access to the EMR system to cross reference. Plus, our EMR system won't allow us to create modules for research. In an effort to streamline our research practice and improve the quality of subject source we're exploring the use of editable source forms (ie, visit 1 source) that can be accessed on an iPad or laptop, have the visit data entered directly into the form and then printed off and placed in the subject's source chart. Future changes or corrections would then be made directly on the paper form (audit trail). We did some test runs in the office and found that it was much easier for the CRCs and physicians to enter data directly onto their iPad/laptop and hit "print" than to try to juggle a lot of paper to complete a study visit. Plus, this trial run proved that electronic form data was "cleaner" and easier to use when it came to data entry. We've talked to a few sponsors who didn't have an opinion either way and the FDA guidelines are vague when it comes to this. My understanding has always been that source is whatever it is - as you mentioned, source can be a Post-It note. Since most sponsors leave it up to the sites to create their source it really comes down - from what I've been told by sponsors - that whatever works best for us. I've been told by sponsors that "source" is a vague term and can be anything from a note that documents the visit as long as it clearly states the data points required for entry into EDC or it can be an elaborately created document with tables, check boxes and flowery verbiage that prompts the CRC to collect this or that. What are your takes on this?

I came across your blog while Googling a particula...

2013-04-04T08:36:43.714-07:00

I came across your blog while Googling a particular question I have that I cannot seem to find any guidance on. Maybe you can shed some light. I'm the Study Manager for our site which is part of a larger medical practice. Our physicians use iPads or laptop to enter patient information into the practice's EMR system. Our research side is "separate" in that we don't utilize the EMR system to log subject information; we use paper forms because - overall - we find it's easier for monitors to review (or at least that's the feedback we get). However, I'm looking at streamlining the research subject experience by reducing unnecessary paperwork for the CRCs and am exploring the use of electronic source for study subjects that would be generated into a hard copy for the subject's source chart. Specifically, we would use an editable form that could be accessed via an iPad or laptop, fill-out during the visit and then simply printed. This printed copy would become the original and any corrections would be made on the paper itself (audit trail). We've discussed this as a practice and as it stands everyone is in favor of this because walking into an exam room with a study patient, being able to whip out an iPad and enter data on the fly that is then printed at the end of the visit and put in the source char is much easier than juggling (at times) a lot of paperwork. We've spoken with some sponsors who haven't said yes or no and the FDA's guidelines are not exactly clear. My understanding is that when it comes down to it source is whatever the site uses - as you said, even a Post-It can be source - and since most sponsors leave source creation up the site I gather we can use this type of electronic source as long as it shows the date, time and person creating it. What are your thoughts? I'd be interested in hearing your take.

This is an excellent blog! I have learnt so much f...

2013-03-24T05:06:00.078-07:00

This is an excellent blog! I have learnt so much from reading the blog! Thank you so much!

Does your website have a contact page? I'm hav...

2013-03-19T11:40:51.946-07:00

Does your website have a contact page? I'm having problems locating it but, I'd like to shoot you an e-mail.
I've got some recommendations for your blog you might be interested in hearing. Either way, great site and I look forward to seeing it grow over time.

Thank you for sharing your tools and experiences. ...

2013-03-07T22:02:35.108-08:00

Thank you for sharing your tools and experiences. As the technology evolves (eCRFs) I can really appreciate how others adapt, increase efficiency and pack as lightly as possible!

these tools could be especially handy for resuming...

2013-03-02T09:52:52.220-08:00

these tools could be especially handy for resuming monitoring across multiple IMVs. These are some of my standard and favorite monitor tools.

Media Monitoring

Hi Jennifer, thanks for clarifying that you intend...

2013-03-01T10:35:05.089-08:00

Hi Jennifer, thanks for clarifying that you intended to write SIV rather than PSSV. Just to elucidate for other readers typically, PSSVs occur as part of site feasibility and before an investigator agreement or IRB submission occurs (since these two activities consume time and resources that the study team would not necessarily devote to a site that has not yet been selected to join the trial).

In this case, you are saying an SIV is occurring after IRB approval and asking, is there a requirement that the Investigator agreement has been executed and Financial Disclosure Forms (FDF) have been collected?

In my experience, I have initiated sites where the investigator agreement is not yet fully executed. This is not a best practice but is sometimes necessary when site startup is time-constrained or extremely condensed and you are doing several start-up steps simultaneously.

Ideally, at the conclusion of an SIV, the Investigational Product should be on site, the IRB approval in place, and the site should be free to enroll. However, without a fully executed investigator agreement, it is absolutely not appropriate to consent subjects because legal issues such as privacy, indemnity, insurance, reimbursements, etc. are not yet fully defined and agreed upon.

So in short, you can perform an SIV without the signed investigator agreement but you should not fully "initiate" the site and allow them to begin the trial yet. I can think of many SIVs I performed where I actually collected the final contract during the visit. Again, completing the investigator agreement after an SIV is a bad and risky practice.

You also asked me about FDFs. I'll probably queue this up as a future blog post as this topic is very misunderstood. Financial Disclosures are only important in the context of a New Drug marketing Application (NDA) submission; we're talking years later after all the supporting trials are done -- not technically at the time of initiation for a particular study.

It is a sponsor's responsibility to assure the agency that investigators did not have undue influence in the trial because of financial interest. The FDF is a form the sponsor keeps to document that they satisfied this requirement and in the NDA they use another mechanism to confirm that it was done.

Example of some other FDF items commonly not understood: if you do a Phase I trial, large open-label safety study or clinical pharmacology trial, FDFs actually aren't technically required and for Phase II, if you read between the lines of CFR part 54.
The sponsor confirms FDF at the end of a study.
The Investigator has the obligation to update the FDF form for up to one year after the trial if anything changes, not the sponsor.

So this is per the regulations, but remember that your work is governed by your SOPs which are actually derived from the regs and guidelines. Always check with your study lead for your trial-specific requirements as they may be more conservative.

Hi Iuliaa, According to ICH E6 GCP Section 8.2.20 a copy of an initiation report should be filed in the Site Master File and Trial Master File.

I've worked at many CROs where we filed a memo/summary of findings, follow-up letter, or abbreviated SIV report to satisfy this guidance and at the sponsor's request. For many simple short trials, the PSSV is completed remotely or even combined with the SIV, and especially in these cases there may be subjective criteria evaluating a Pi's past performance in other trials; this is not something you would necessarily want to share with the site you are starting a relationship with. I hope that clarifies. The guidelines really just suggest that you document a) that the site is suitable to conduct the trial and b) that trial procedures were reviewed with the investigator and the
investigator’s trial staff prior to initiating the trial.

Hi and thanks for a great comment. I agree that r...

2013-03-01T09:20:43.292-08:00

Hi and thanks for a great comment. I agree that regulators would prefer not to see sponsor provided source. If a PI is truly involved in the trial and understands the protocol they should be willing and able to implement their own source documents. From a monitoring perspective, if many sites use similar source there is some efficincy to be gained but you have to balance that against the risk that something has been inadvertently left out. I discuss this topic further in a post from Apr-2011 on Sponsor Furnished Source Documents.

Thanks for a great blog topic suggestion. Please ...

2013-02-28T21:27:33.489-08:00

Thanks for a great blog topic suggestion. Please check out my Feb-2012 post about the monitoring tools & notes I like to use during SDV.

I am wondering if you have sample worksheets monit...

2013-02-27T21:28:43.618-08:00

I am wondering if you have sample worksheets monitors can use during SDV on site as this will also help capture everything the site might be missing

I'm sorry SIV...Thank you, Jennifer

2013-02-20T13:39:20.189-08:00

I'm sorry SIV...Thank you, Jennifer